A New PRNP Mutation (G131V) Associated With Gerstmann-Sträussler-Scheinker Disease

Abstract

This is the first mutation described in the short, antiparallel beta-sheet domain of the prion protein. This report highlights the importance of genetic analysis of patients with atypical dementia even in the absence of a family history.

Unfolding, Aggregation, and Amyloid Formation by the Tetramerization Domain from Mutant p53 Associated with Lung Cancer

“…However, this amino acid change is in the middle of an extended turn rather than between an α-helix and a β-strand. A mutation that causes a valine-for-glycine change also is associated with Gerstmann-Straussler-Scheinker syndrome, a rare form of prion disease (58). Our study thus provides complementary further evidence for the existence of a linkage between mutations that change Gly to Val and the formation of misfolded amyloid proteins, and it highlights the importance of a molecular classification of disorders associated with protein misfolding.…”

Water molecules as structural determinants among prions of low sequence identity

“…1A) [17]; additionally it makes a H-bond with the Q217(H3) sidechain (TSE sensitive [30]). Other residues also participate in the binding-site framework: the sidechain of Q160 prevents the natural elongation of the b-sheet by interacting with the carbonyl of G131 (b1, TSE sensitive [31]), and preventing the extension of the b-sheet to the V161 peptide. Moreover R220 sidechain interacts with S132 OG sustaining the bulge promoted by the G131 (Fig.…”

“…1). In addition, localized human pathological mutations like the G131V [31,34] (Creutzfeldt-Jakob disease) and Q217R [30,35] (Gerstmann-Sträussler syndrome) are known; these mutations are likely to exert a disruptive influence on the bulge (as shown by the Q217R MD simulation [17]). …”

Prion Proteins with Different Conformations Accumulate in Gerstmann-Sträussler-Scheinker Disease Caused by A117V and F198S Mutations

“…3 GSS is caused by mutations P102L, P105L, A117V, G131V, F198S, D202N, Q212P, and Q217R in PRNP. 3,11,12 The pathological hallmark of GSS is the accumulation of PrP, with and without amyloid tinctorial properties, in the brain. 3 Our studies have shown that the pattern of PrP sc isoforms in the multiple GSS variants analyzed is different from that seen in CJD.…”

“…3 Our studies have shown that the pattern of PrP sc isoforms in the multiple GSS variants analyzed is different from that seen in CJD. [11][12][13] Patients with CJD present full-length and Ntruncated PrP fragments whereas patients with GSS present full-length as well as N-and C-terminal truncated PrP peptides. 10 -13,14,15 Previous studies showed that the amyloid subunit in GSS F198S is a 7-kd peptide with an N terminus at residue G 81 .…”